Magnetic MicroRNAs Could Help Treat Incontinence

Rectoanal incontinence and constipation are conditions which severely lower quality of life for sufferers and yet are poorly addressed by modern medicine. This is partly due to a lack of reporting by patients, and partly because these conditions tend to afflict people dealing with a wide range of health issues. In nursing homes, the percentage of residents suffering from faecal incontinence approaches 50%. A new therapy, which uses the unlikely combination of microRNAs and magnetism, might offer patients a solution to this unpleasant and understudied condition. Researchers at Thomas Jefferson University used microRNAs targeting the Rho/ROCK pathway to modulate the muscle tone of mice, relieving constipation or incontinence as needed.

Incontinence and constipation both affect the internal anal sphincter, a ring of muscle around the anal opening. The sphincter is made of smooth muscle, which contracts and relaxes without conscious effect. This muscle weakens with age, and when factors such as dementia compound the problem, bowel movements can become uncontrollable in the elderly, leading to faecal incontinence. Constipation, while merely a nuisance for many patients, becomes intractable for others. Constipation-related hospital admission in the USA more than doubled from 1997-2010. This is partly due to the so-called opioid epidemic sweeping the country, where more than 250 million opioid prescriptions were given out in 2012, and 90% of patients with moderate to severe pain are given opioids. Opioid related constipation has been estimated to affect 80% of all chronic pain sufferers.

Clearly, a solution is needed.

A Solution for Incontinence and Constipation?

Professor Satish Rattan, of the Department of Medicine at the Sidney Kimmel Medical College of Thomas Jefferson University, based the study on his lab’s previous work that had shown the Rho/ROCK gene pathways could modulate smooth muscle tone.

MicroRNAs can modulate gene expression by targeting messenger RNAs before they can be translated into proteins. Injecting microRNAs can target specific areas of the body, but this runs the risk of spreading from the area of injection and having systemic effects. Instead, Rattan’s lab injected the microRNAs alongside a formulation of miniscule metal beads. Then, a magnet was surgically added to the anal region to create a magnetic field, which held the microRNA/bead mix in place. This process proved extremely effective at keeping the microRNAs isolated to the target region, which had the effect of relaxing or contracting the smooth muscle as required.

Professor Rattan, who led the study alongside Drs. Jagmohan Singh and Ipsita Mohanty, said “The key impact of this work is that this novel approach may be an efficient way of gene delivery, and since it is topical delivery at the affected site, is expected to have limited systemic effects.”

Although highly promising, the technology still has some hurdles to bypass before any clinical trials on human patients can be started.

“These studies do not address the issue of toxicity because of the acute nature of the experiments. Such studies will require monitoring of a number of cardinal signs in the animals for three to four weeks,” said Rattan. “The next step should be to carry out chronic experiments where the animals need to be monitored for several weeks following their blood pressures, EKG, body weight and the bowel movement etc.”

Nevertheless, the technology has great potential, partly through being adaptable to other organs where localised, non-systemic miRNA targeting is required, such as for stomach sphincters that become dysfunctional during acid reflux. It represents another example of the potential of RNA therapies in modern medicine.

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